The transient kinetics of guanine nucleotide activation of adenylate cyclase has been modeled with the SAAM modelling program. The model developed extends the previously reported three state model and provides an explanation for the differences both in effectiveness and kinetics observed with GTP and Gpp(NH)p. In essence, the model suggests that, in addition to the catalytic site that converts ATP to cyclic AMP, the enzyme system contains a GTPase at the nucleotide regulatory site that converts GTP to inactive product, GDP. One important outgrowth of the model is that it serves to explain the rapidly reversible dynamic features of hormone and GTP activation of adenylate cyclase. As related in a separate report, it also serves to explain the actions of cholera toxin on adenylate cyclase systems.